Ocular malignant melanoma and blue nevi.
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Biomedical subjects
Publications and source records attributed to M T Lopez.
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In a randomized, controlled study, the efficacy and safety of two different schemes of albendazole therapy for treatment of porcine cysticercosis were tested. Seventeen naturally infected pigs were divided into three groups and treated per os with albendazole (50 mg/kg single dose), albendazole (30 mg/kg every day for three days), or given no treatment, respectively. Serologic responses were monitored with the enzyme-linked electroimmunotransfer blot assay. Pigs were humanely killed 12 weeks after treatment, necropsied, and the number of parasites was recorded. Scolex evagination was used to assess viability of the cysts. Both albendazole-treated groups had significant side effects (anorexia, lethargy). Only a single viable cyst was recovered from the brain of one animal after therapy in the multiple-dose group, and the single-dose therapy left 11% of the cysts viable. In contrast, more than 90% of muscle cysts were found to be viable in the untreated group. Although albendazole therapy for three days was found to be highly effective, side effects and the need for multiple doses would still prevent its widespread use.
The association between multiple sclerosis (MS) and alleles of the HLA class II genes indicates that at least one MS susceptibility gene is linked to the HLA class II region. However, the actual locus responsible has not been precisely identified. The recent cloning of new genes involved in antigen processing that map within the HLA class II region led us to investigate--using the restriction fragment length polymorphism (RFLP) technique and sequence-specific oligonucleotide analysis--whether these genes might play a role in conferring susceptibility to MS. We studied large multifunctional protease (LMP) 2 and 7 and transporter associated with antigen processing (TAP) 1 and 2 gene polymorphisms in 60 HLA-DR2 MS patients and 60 HLA-DR2 healthy subjects and found no specific or preferential RFLP patterns or coding sequence variants in the patient group. Our data do not support a role for these genes in MS susceptibility.
Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes.
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The ability to discriminate between self and nonself antigens is vital to the functioning of the immune system as a specific defense against invading microorganisms. Failure of the immune system to "tolerate" self tissues can result in pathological autoimmune states leading to debilitating illness and sometimes death. The induction of autoimmunity involves genetic and environmental factors that have focused the attention of researchers on the trimolecular complex formed by major histocompatibility complex molecules, antigen, and T cell receptors. Detailed molecular characterization of these components points to potential strategies for disease intervention.
Considerable information concerning the serology and biochemistry of antigen-specific, T cell-derived suppressor factors has been obtained with the use of T cell hybridomas as a source of homogeneous material. Similarly, knowledge of helper T cell products and receptors is accumulating from studies of helper T cell clones and hybridomas. Our strategy for studying the mechanisms by which suppressor factors inhibit responses was to determine whether monoclonal suppressor factors could inhibit antibody responses specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in cultures containing unprimed splenic B cells, macrophages, and GAT-specific T cell clones as a source of helper activity. The MHC-restricted, two chain suppressor factors, GAT-TsF2, inhibited these responses if the helper T cell clones and suppressor factor were derived from H-2-compatible mice. Furthermore, responses were inhibited by briefly pulsing T cell clones with GAT-TsF2 in the presence of GAT, indicating that suppressor factors need not be present continuously. In addition, helper T cell clones adsorbed syngeneic, but not allogeneic, GAT-TsF2 in the presence of GAT. Adsorption also requires a shared antigenic specificity between the H-2b-derived helper T cells and TsF2 factor. Thus, helper T cells can serve as the cellular target of antigen-specific, MHC-restricted GAT-TsF2, and cloned helper T cells can be used as a homogeneous target population for analysis of the molecular mechanisms of T cell suppression.
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